When World War II threatens to shut down Major League Baseball, candy magnate and Cubs owner Walter Harvey (Garry Marshall) persuades his fellow owners to bankroll a women's league. Ira Lowenstein (David Strathairn) is put in charge, and Ernie Capadino (Jon Lovitz) is sent out to recruit players. Capadino attends an industrial-league softball game in rural Oregon and likes what he sees in Dottie, the catcher for a local dairy's team. Dottie turns down Capadino's offer, happy with her simple farm life while waiting for her husband Bob (Bill Pullman) to come back from the war. Her sister (and teammate) Kit (Lori Petty), however, is desperate to get away and make something of herself. Capadino is not impressed by Kit's hitting performance, but agrees to take her along if she can change Dottie's mind. Dottie agrees, but only for her sister's sake.

The Peaches are managed by Jimmy Dugan (Tom Hanks), an alcoholic former marquee Cubs slugger who initially treats the whole thing as a joke, unconvinced that women are capable of being decent ball players. The league attracts little interest at first. With a Life magazine photographer in the stands, Lowenstein begs the players to do something spectacular in hopes that a magazine article will attract interest in the league. Dottie obliges when a ball is popped up behind home plate, catching it while doing a split. The resulting photograph makes the magazine's cover. A publicity campaign and random demeaning stunts (such as offering kisses from the players for catching foul balls) draws more people to the ballgames, but the owners remain unconvinced. Lowenstein, firm in his belief in the teams' success, proposes to Mr. Harvey to take over the league if it continues to do well. Meanwhile, Kit's sibling rivalry with her sister results in her getting angry after she is taken out of a game, and ultimately, she ends up in a physical confrontation with Doris. Lowenstein speaks to Dottie afterwards, as Dottie is prepared to leave due to her frustrations with Kit. Instead, Kit is traded to the Peaches' rival, the Racine Belles.

The Peaches end the season qualifying for the league's World Series. In the locker room, Jimmy gives Betty a telegram that informs her her husband was killed in action in the Pacific Theater. The grief-stricken Betty leaves the team. Later that evening, Dottie receives a surprise when Bob, who was serving in Italy, shows up, and tells her he has been discharged from the Army due to getting injured. The following morning, Jimmy discovers that Dottie is going home with Bob. He is unable to persuade her to at least play in the World Series; he tells her she will regret her decision.

The Peaches and Belles meet in the World Series, which reaches a seventh and deciding game. Dottie, having reconsidered on the drive back to Oregon, returns as catcher for the Peaches for the final game, while Kit is the starting pitcher for the Belles. With the Belles leading by a run in the top of the ninth, Dottie drives in the go-ahead run. Kit is the final batter. Under immense pressure, she gets a hit and, ignoring the third base coach's sign to stop, scores the winning run by knocking her sister over at the plate and dislodging the ball from Dottie's hand. The sellout crowd convinces Harvey to give Lowenstein the owners' support. After the game, the sisters reconcile before Dottie leaves.

Back in the present, Dottie is reunited with several other players, including Kit, whom she has not seen in several years. The fates of several of the characters are revealed: Jimmy, Bob, and Evelyn have all died, while Marla has been married to Nelson, a man she met in a bar, for over 40 years. The original Peaches sing a team song composed by Evelyn and pose for a group photo.

On MLB Network's Costas at the Movies in 2013, director Penny Marshall talked about her initial interest in Demi Moore for the part of Dottie Hinson, saying: "Demi Moore, I liked, but by the time we came around, she was pregnant."[3]

Discussing the skirts they wore playing baseball in the film, Geena Davis said on MLB Network's Costas at the Movies in 2013, "Some of our real cast, from sliding into home, had ripped the skin off their legs. It was nutty."[4]

The film was released on July 1, 1992 and was #1 by its second weekend (July 10–12).[5] It was a commercial success, making $107 million in the United States (and an additional $25 million worldwide) on a $40 million budget, and was well received by critics.[6][7][8][9][10]

With 2012 marking the 20th year since the film's release, A League of Their Own was released as a 20th Anniversary Edition Blu-ray on October 16, 2012.[17]

Forty-seven former players of the AAGPBL reunited in New York to celebrate the film and the real women who inspired it. Events included a trip to Cooperstown for a special program at the National Baseball Hall of Fame, reminiscent of the film's final scene depicting members of the AAGPBL and family coming together to witness the honoring of the Women's Professional Baseball League. The reunion wrapped up with a game of softball held at Alliance Bank Stadium in nearby Syracuse.[18]